Influence of the vitamin D hormonal status on the hepatic response to bromobenzene

P. Haddad, P. A. Coulombe, M. Gascon-Barre

Research output: Contribution to journalArticlepeer-review

Abstract

Hypocalcemic vitamin D-depleted rats received either 1,25-dihydroxy-vitamin D3 [1,25(OH)2D3] or calcium p.o. in order to study the effects of plasma calcium normalization, resulting from hormone or dietary calcium administration, on the hepatic response to bromobenzene (BB). Results showed that 1,25(OH)2D3 administration induced a rise in the circulating aspartate aminotransferase, alanine aminotransferase and sorbitol dehydrogenase after BB administration significantly greater than in unsupplemented rats. The volumic density of necrosis was not, however, increased by 1,25(OH)2D3 whereas the proportion of acidophilic cells surrounding the necrotic area and the ratio of acidophilic to necrotic cells were significantly increassed suggesting the presence of regenerating parenchyma. Oral calcium yielded an increase comparable to that of 1,25(OH)2D3 in apparent BB toxicity which was accompanied by a significant rise in both the volumic density of necrosis and of acidophilic cells but the ratio of acidophilic to necrotic cells was not increased by dietary calcium. The amount of cytochrome P-450 lost after BB administration, the covalent binding of BB metabolites to cellular proteins in vitro and the total liver glutathione content were not changed by either 1,25(OH)2D3 or calcium supplementation. Results show that hypocalcemic vitamin D-depleted rats are protected partially against BB toxitiy; this protection does not seem to be due to a decrease in the hepatic metabolism of BB but seems to be related to the hypocalcemic state; on the other hand, the active regenerating process which seemed more apparent in 1,25(OH)2D3-treated than in all other animals may have contributed to offset partly the cellular damage induced by the toxin in the hormone-treated group.

Original languageEnglish (US)
Pages (from-to)354-363
Number of pages10
JournalJournal of Pharmacology and Experimental Therapeutics
Volume242
Issue number1
StatePublished - Jan 1 1987

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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